ENGOT-EN3-NSGO/PALEO

Nordic Society of Gynaecological Oncology - Clinical Trial Unit (NSGO-CTU)

Blegdamsvej 9, Copenhagen OE, Denmark, 2100

Mansoor Raza Mirza, Nordic Society of Gynaecological Oncology - Clinical Trial Unit (NSGO-CTU), 45 35459624, Mansoor.Raza.Mirza@Regionh.dk

Mansoor Raza Mirza, Nordic Society of Gynaecological Oncology - Clinical Trial Unit (NSGO-CTU) , 45 35459624, Mansoor.Raza.Mirza@Regionh.dk

No

No

No

Final

01 Nov 2020

Yes

01 Nov 2020

Yes

29 Apr 2022

No

The overall objective is to obtain preliminary evidence of efficacy of palbociclib-letrozole combination vs. placebo-letrozole combination therapy in the treatment of ER+ advanced or relapsed endometrial cancer. The primary objective is evaulation of Progression-Free Survival (PFS) in patient cohorts receiving either palbociclib-letrozole vs. placebo-letrozole for treatment of ER+ advanced or relapsed endometrial cancer.

All study subjects were required to read and sign the informed consent form. The IDMC was established to provide independent review and assessment of the efficacy and safety data in a systematic manner and to safeguard the interest and safety of the participating patients in the study. The IDMC consisted of 3 independent individuals, and made recommendations to the sponsor, based on their review, to continue or stop the trial based on their assessment of safety information. The trial was conducted in accordance with the ethical principles of the Declaration of Helsinki and the ICH-GCP guidelines. The local principal investigators were responsible for ensuring that the trial was conducted in accordance with the protocol, the ethical principles of the Declaration of Helsinki, current ICH guidelines on GCP and applicable local regulatory requirements.

16 Feb 2017

Yes

Yes

Norway: 6

Spain: 20

Finland: 3

Germany: 22

Denmark: 22

73

73

0

0

0

0

0

0

29

44

0

Overall period

Randomised - controlled

Palbociclib and placebo treatment was blinded. The trial medication was labeled using a unique Lot-ID, which was linked to the randomization scheme. The active and placebo capsules were identical and presented in the same packaging to ensure blinding of the study medication.

Yes

Letrozole

Tablet

Oral use

Tablet Letrozole 2,5 mg taken orally once daily on days 1-28 in each 28 day cycle.

Placebo

Capsule

Oral use

One placebo capsule orally once daily on days 1-21 in a 28 days cycle.

Palbociclib

Capsule

Oral use

One palbociclib capsule (125 mg/capsule) orally once daily on days 1-21 in a 28 days cycle.

Letrozole

Tablet

Oral use

Patients receive tablet letrozole 2.5 mg orally once daily on days 1-28 in a 28 days cycle.

Arm A

Arm B

Arm A

Arm B

The progression events are defined by well-documented and verifiable imaging data. PFS was censored if the patient was lost to follow-up or refused to continue in the trial (i.e. withdraws consent). For patients alive and without progression at the time of analysis, PFS was censored. In any case of censoring, the date of censoring was the last time point documenting survival status.

Primary

The PFS is calculated as time elapsed from date of randomization to date of progression or death of disease, whichever is the first registered event.

PFS between arms was compared using the log rank test, the hazard ratio was estimated using cox-regression including the stratification factors: Number of prior chemotherapy lines, measurable versus evaluable disease, and prior medroxyprogesterone/megestrol acetate treatment

Arm A v Arm B

73

Pre-specified

0.71

2-sided

Standard error of the mean

0.189

ORR according to Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1). ORR is determined as the rate of patients with an observed tumour response. Best overall response is the best response (CR, PR, SD, PD) recorded from the start of treatment until disease progression taking as reference for progressive disease the smallest measurements recorded since the treatment started.

Secondary

ORR is recorded from the start of treatment until disease progression.

The percentage of patients in the treatment arm, which achieve complete response (CR) or partial response (PR) or stable disease (SD) for at least 12 weeks, assessed according to RECIST 1.1 criteria.

Secondary

From start of treatment until end of follow-up.

TFST is defined as the time from start of treatment until initiation of subsequent-line of anti-cancer treatment or death. TFST was censored if the patient was lost to follow-up or refused to continue in the trial (i.e. withdraws consent). For patients alive and without initiation of third-line treatment at the time of analysis, TFST was censored. In any case of censoring, the date of censoring was the last time point documenting survival status.

Secondary

Time from randomization to first subsequent treatment or death of disease, whichever is the first registered event.

PFS2 is defined as the time elapsed from date of randomization to date of 2nd progression or death of disease, whichever is the first registered event. PFS2 was censored if the patient was lost to follow-up or refused to continue in the trial (i.e. withdraws consent). For patients alive and without progression at the time of analysis, PFS2 was censored. In any case of censoring, the date of censoring was the last time point documenting survival status.

Secondary

Time from randomization to second subsequent disease progression or death.

TSST is defined as the time from start of treatment until initiation of anti-cancer treatment for second subsequent progression of disease or death. TSST was censored if the patient was lost to follow-up or refused to continue in the trial (i.e. withdraws consent). For patients alive and without initiation of fourth-line treatment at the time of analysis, TSST was censored. In any case of censoring, the date of censoring was the last time point documenting survival status.

Secondary

Time from randomization to second subsequent therapy or death.

Quality of Life (QoL) scores, assessed by the "European Organisation for Research and Treatment of Cancer- Quality of Life Questionnaire - C30" (EORTC-QLQ-C30), calculated using the EORTC scoring manual. Scores were calculated for each individual patient at selected visits. First part: 28 questions on difficulties in everyday life. Scores from 1 to 4; 1 = "Not at all", 2 = "A little", 3 = "Quite a bit", 4 = "Very much". Second part: 2 questions on general health and QoL self-assessment: scores from 1 to 7; 1 = "Very poor", 7 = "Excellent". Reported values for Time 1-10 are mean overall QoL measures normalised to a number from 0-100, where a high score indicates high QoL. The unit for Time 1-10 is 'months'.

Secondary

QoL scores assessed before treatment until 6 months after end of treatment.

The percentage of people in each of the two treatment arms, who are still alive 3,5 years after randomization. OS is defined as the time from the date of randomization to the date of death, regardless of the cause of death. Patients who were alive at the time of the analysis were censored at the date of their last follow-up assessment. Patients without follow-up assessment were censored at the day of their last dose and patients with no post baseline information were censored at the time of their first administration of treatment drugs.

Secondary

OS was assessed from end of treatment until death or 42 months after randomization.

Progression-free survival in the subgroup of patients with primary advanced disease.

Secondary

Time from date of randomization to date of progression or death.

Progression-free survival in the subgroup of patients with 1st relapse of disease.

Secondary

Time from date of randomization to date of progression or death.

Progression-free survival in the subgroup of patients with 2nd or more relapses of disease.

Secondary

Time from date of randomization to date of progression or death.

PFS in the subgroup of patients with measurable disease according to RECIST 1.1.

Secondary

Time from date of randomization to date of progression or death.

PFS in the subgroup of patients with evaluable disease according to RECIST 1.1.

Secondary

Time from date of randomization to date of progression or death.

PFS in the subgroup of patients that recieved no prior endocrine treatment.

Secondary

Time from date of randomization to date of progression or death.

PFS in the subgroup of patients that recieved one line of prior endocrine treatment. Patient may have received maximum one line of endocrine therapy containing MPA/Megace.

Secondary

Time from date of randomization to date of progression or death.

Quality of Life (QoL) scores, assessed by the "European Organisation for Research and Treatment of Cancer- Quality of Life Questionnaire – EN24" (EORTC-QLQ-EN24), calculated using the EORTC scoring manual. This questionnaire is designed for patients with endometrial cancer. Scores were calculated for each patient at selected visits. QLQ-EN24 incorporates 5 multi-item scales to assess lymphoedema, urological symptoms, gastrointestinal symptoms, body image and sexual/vaginal problems. In addition, 8 single items assess pain in back and pelvis, tingling/numbness, muscular pain, hair loss, taste change, sexual interest, sexual activity and sexual enjoyment. Scores from 1 to 4; 1 = "Not at all", 2 = "A little", 3 = "Quite a bit", 4 = "Very much". Reported values for Time 1-10 are mean scores for gastrointestinal symptoms normalized to a number from 0-100, where a high score represents a high level of symptomatology. The unit for Time 1-10 is 'months'.

Secondary

QoL scores assessed before treatment until 6 months after end of treatment.

The investigator must report all adverse events from first dose until 28 days after the last dose of treatment drugs. The AEs must be documented in the eCRFs. Concomitant illnesses, which existed before entry into the trial, will not be considered AEs.

Concomitant illnesses, which existed before entry into the trial, will not be considered AEs unless they worsen during the treatment period. Pre-existing conditions will be recorded in the eCRF on the Medical History or appropriate page.

4.0

Arm A

Arm B